Tuberculosis is a major threat to global health and one of the major causes of death from infectious disease. One-third of the world's population is latently infected with M. tuberculosis (MTB). Most cases of active disease will arise from this enormous reservoir of latent TB, resulting in further spread of the disease, which embodies a major obstacle in achieving worldwide control of TB (WHO, 2011). Current diagnostics cannot distinguish between active and latent infection, and the only available vaccine against TB has limited efficacy. Further the increasing incidence of drug resistant strains has prompted their inclusion in the list of A-C pathogens, and heightened interest in development of effective vaccines. Therefore, there is a need for the development of novel vaccines and diagnostic strategies (Wallis et al., 2010).
Human T cell responses to MTB involve CD4+, CD8+ and γ∂ T cells (Boom, 1996). CD4 T cells have been shown to be central to the defense against MTB through the discovery that HIV infected patients are more susceptible to primary TB infection, re-infection and re-activation (Barnes et al., 1991). Different types of CD4 T helper (Th) cells develop from naïve T cells under the influence of polarizing signals and master transcription factors. Seminal studies showed that human memory T cells directed against MTB secreted IFN-γ, thus representing the human counterpart of mouse Th1 cells (Del Prete et al., 1991). IFN-γ has an essential role in the protective immunity to mycobacteria, as demonstrated by the increased susceptibility to mycobacteria in individuals with genetic defects in the IFN-γ receptor (Newport et al., 1996). Furthermore, different Th cell subsets differ in expression of chemokine receptors and therefore in migratory capacity and tissue localization (Sallusto et al., 2000). Th1 cells mainly express CCR5 and CXCR3 (Sallusto et al., 1998), while Th17 cells co-express CCR6 and CCR4 and Th22 cells co-express CCR6 and CCR10 (Acosta-Rodriguez et al., 2007; Duhen et al., 2009)
The MTB genome encodes more than 4,000 different ORFs, generally highly conserved amongst different strains, including drug resistant ones. Yet, only a handful of them have been reported as targets of human CD4+ T cells, the key cellular effector of MTB immunity. A genome-wide study determining which MTB antigens are immunodominant is to date lacking.